Purinostat Mesylate Combined With Pomalidomide Capsules and Low-dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

NCT06484829 | Recruiting Phase 1

• 1 other identifier: ZLPM-002-1.0
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Purpose Phase Ib. To determine the Maximum Tolerated Dose (MTD) and establish the Recommended Phase IIa Dose (RP2D) of Purinostat Mesylate for Injection combined with fixed-dose Pomalidomide Capsules and Dexamethasone in patients with relapsed or refractory multiple myeloma. Phase IIa. To further evaluate the safety and tolerability of Purinostat Mesylate for Injection at the RP2D combined with fixed-dose Pomalidomide Capsules and Dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM). Secondary Objectives Phase Ib

1. 1.To evaluate the safety and tolerability of Purinostat Mesylate for Injection combined with fixed-dose Pomalidomide Capsules and Dexamethasone in the treatment of relapsed or refractory multiple myeloma.
2. 2.To assess the pharmacokinetic (PK) parameters of the combination therapy in patients with relapsed or refractory multiple myeloma.
3. 3.To observe the preliminary efficacy of the combination therapy in patients with relapsed or refractory multiple myeloma.
4. 4.To evaluate the preliminary efficacy of the combination therapy in patients with relapsed and refractory multiple myeloma (RRMM).
5. 5.To characterize the population pharmacokinetic (PPK) profile of the combination therapy in patients with relapsed or refractory multiple myeloma (RRMM).

Conditions

Relapsed or Refractory Multiple Myeloma (RRMM)

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity (DLT)

  One or more unacceptable toxic reactions following administration of the drug, resulting in the inability to continue increasing the dose or prolonging the dosing cycle

  Day 21/Day 28

• Maximum Tolerated Dose (MTD)

  The maximum dose or concentration of a drug that does not cause death in experimental animals in experiments other than acute toxicity animal experiments (short-term repetitive experiments, subchronic toxicity experiments, chronic toxicity experiments).

  Day 21/Day 28

• Objective remission rate (ORR)

  Defined as the proportion of subjects achieving a strict complete remission (sCR) + complete remission (CR) + very good partial remission (VGPR) + partial remission (PR);

  Day 21/Day 28

Secondary Outcomes (5)

• Complete Remission Rate (CRR)

  Day 21/Day 28

• Duration of efficacy (DOR)

  Day 21/Day 28

• Time to Relief (TTR)

  Day 21/Day 28

• Progression-free survival (PFS)

  Day 21/Day 28

• Overall survival (OS)

  Day 21/Day 28

Study Arms (2)

A group

EXPERIMENTAL

A: Treatment Cycle Regimen - Regimen A (2-Week On/1-Week Off) - 21-Day Cycle Purinostat Mesylate for Injection: Intravenous infusion on Days 1, 4, 8, and 11 of each 21-day (3-week) cycle during the Continuation Dosing Phase Ib and Phase IIa; Pomalidomide Capsules: Oral administration once daily at 4 mg for 14 consecutive days followed by a 7-day rest period, with each cycle lasting 21 days (3 weeks); Dexamethasone Acetate Tablets: 20 mg orally administered on Days 1, 4, 8, and 11 of each treatment cycle.

Drug: Purinostat Mesylate 4 mg/m2; Drug: Purinostat Mesylate 6 mg/m2; Drug: Purinostat Mesylate 8.4 mg/m2

B group

EXPERIMENTAL

B: Treatment Cycle Regimen - Regimen B (3-Week On/1-Week Off) - 28-Day Cycle Purinostat Mesylate for Injection: Intravenous infusion on Days 1, 4, 15, and 18 of each 28-day (4-week) cycle during the Continuation Dosing Phase 1b and Phase IIa; Pomalidomide Capsules: Oral administration once daily at 4 mg for 21 consecutive days followed by a 7-day rest period, with each cycle lasting 28 days (4 weeks); Dexamethasone Acetate Tablets: 20 mg orally administered on Days 1, 4, 15,and 18 of each treatment cycle.

Drug: Purinostat Mesylate 4 mg/m2; Drug: Purinostat Mesylate 6 mg/m2; Drug: Purinostat Mesylate 8.4 mg/m2

Interventions

Purinostat Mesylate 4 mg/m2 DRUG

4 mg/m2 Purinostat Mesylate + 4mg Pomalidomide + 20mg Dexamethasone.

A group; B group

Purinostat Mesylate 6 mg/m2 DRUG

6 mg/m2 Purinostat Mesylate + 4mg Pomalidomide + 20mg Dexamethasone.

A group; B group

Purinostat Mesylate 8.4 mg/m2 DRUG

8.4 mg/m2 Purinostat Mesylate + 4mg Pomalidomide + 20mg Dexamethasone.

A group; B group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with multiple myeloma (MM) by reference to the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of Multiple Myeloma (Revised 2022);
• Those who have received at least one line of prior systemic antimyeloma therapy (which must include lenalidomide and proteasome inhibitors; see Appendix 4 for counts of myeloma treatment lines) and meet the definition of relapse or refractory; Definition of relapse: disease progression that occurs at least 60 days from the last treatment after the efficacy of a prior treatment regimen was evaluated at MR or better (except for those who relapsed more than 1 year after treatment); Definition of refractory: progression during prior therapy or progression within 60 days of the last treatment; or failure to achieve MR or better after at least 2 prior courses of therapy; or treatment intolerance.
• Age 18-75 years, male or female, if of childbearing potential subjects should be on effective contraception and must agree to comply with all contraceptive requirements:
• \) Females of childbearing potential must agree to and comply with the contraceptive measures specified in the protocol: beginning 4 weeks prior to treatment with this product, two reliable methods of contraception are required concurrently for the duration of the treatment, during the dose suspension, and for 4 weeks after termination of the treatment (one highly effective method of contraception-tubal ligation, intrauterine device, hormonal (contraceptive pills, injections, patches, vaginal rings, or implants), or partner's vasectomy, and another effective contraceptive method - male rubber or synthetic condom, diaphragm or cervical cap). Effective contraception is needed even with a history of infertility unless due to hysterectomy; 2) Men of childbearing potential must use a rubber or synthetic condom at all times during sexual contact with women of childbearing potential beginning 4 weeks prior to treatment with this product, during the treatment period, during the dose suspension period, and for 4 weeks after termination of treatment, even if they have had a successful vasectomy; 4. Subjects with multiple myeloma who have measurable M protein, i.e., at least one of the following 3 measurements:
• Serum M protein ≥ 0.5 g/dL (5 g/L);
• Urine M protein ≥ 200 mg/24h;
• Serum free light chain assay: in the case of an abnormal serum free light chain ratio (less than 0.26 or greater than 1.65), an affected free light chain level ≥10mg/dL (100mg/L); 5. Hematologic fulfillment of the following conditions:
• \) ANC ≥ 1.0 x 109/L (without granulocyte colony-stimulating factor within 7 days), with no specific requirement for neutrophil count when ≥ 50% of the bone marrow is plasma cells; 2) PLT ≥75 × 109/L (no platelet transfusion or use of thrombopoietin within 7 days), and platelets ≥50 × 109/L were eligible for enrollment when ≥50% of plasma cells were present in the bone marrow; 3) Hemoglobin ≥ 80 g/L (no red blood cell suspension infusion or use of erythropoietin within 7 days); 6. Liver and kidney function tests fulfill the following conditions:
• TBIL ≤ 1.5 x ULN;
• ALT and AST are ≤ 2.5 x ULN;
• Glomerular filtration rate (GFR) ≥ 30mL/min/1.73m2 (Cockcroft-Gault formula) without the effects of dialysis therapy; 7. Ability to receive and have access to antithrombotic medications such as low molecular heparin sodium, heparin, warfarin or aspirin; 8. An ECOG (Appendix 2) score of 0-2 and an expected survival of ≥12 weeks; 9. Subjects voluntarily enrolled in the study and signed an informed consent form.

You may not qualify if:

• Those with prior antitumor therapy with histone deacetylase (HDAC) inhibitors (except cedarbenazine), antibody-coupled degradation agents (DAC), HSP90 inhibitors, or valproic acid; or those who, in the judgment of the investigator, are intolerant to treatment with the same type of drug as HDAC inhibitors, pomalidomide, thalidomide, lenalidomide, or the like (e.g., grade ≥3 rash during prior use, severe refractory myelosuppression, etc.);
• Those with disease progression following prior treatment with standard dose pomalidomide;
• Allergic reactions to the components of the test drug involved in this trial;
• A diagnosis of non-secretory MM (defined as a subject who is completely non-secretory or who has a small amount of free light chain but the affected light chain is less than 100 mg/L), or MM in combination with amyloidosis, or plasma cell leukemia, either primary or during the course of therapy
• Those with active new thrombosis or who are unable to receive antithrombotic therapy;
• Other malignant tumors within 5 years prior to screening, with the exception of cured carcinoma in situ (e.g., cervix, breast, bladder, etc.), basal cell carcinoma of the skin, squamous epithelial cell carcinoma of the skin, or early-stage prostate carcinoma (with clinical staging of Tla or T1b);
• Those who have a combination of central nervous system disorders and require treatment for such disorders
• Peripheral neuropathy ≥ grade 3; and
• Co-morbidities requiring long-term treatment with immunosuppressive drugs or steroids; 10. active infectious diseases;
• Those with comorbid active infectious diseases, including the following:
• \) Hepatitis B Surface Antigen (HbsAg) or Hepatitis B Core Antibody (HbcAb) positive with HBV-DNA quantification higher than the upper limit of normal value 2) Positive Hepatitis C Virus Antibody (HCV-Ab) with HCV RNA quantification above the upper limit of normal; 3) Human immunodeficiency virus antibody (HIV-Ab) or anti-syphilis spirochete antibody (TP-Ab) positive; 11. Subjects with any of the following:
• Cardiac insufficiency ≥ grade 3 by NYHA classification (Appendix 1) criteria;
• Myocardial infarction within 6 months;
• Poorly controlled angina, including variant angina, within 6 months;
• Clinically significant arrhythmia;

Sponsors & Collaborators

• Chengdu Zenitar Biomedical Technology Co., Ltd: lead

Study Sites (1)

West China Hospital Sichuan University

Chengdu, Sichuan, 610000, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ting Niu, Doctor

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liangkun Sun, bachelor

CONTACT

15885742617; liangkunsun@zenitar.cn

Zheng Jiang, bachelor

CONTACT

19048075294; zhengjiang@zenitar.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2024
• First Posted: July 3, 2024
• Study Start: March 25, 2024
• Primary Completion: February 1, 2026
• Study Completion: April 1, 2026
• Last Updated: April 2, 2025

Record last verified: 2025-03

Locations

CN (1)